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Combined effects of Notch signaling and cytokines induce a multiple log increase in precursors with lymphoid and myeloid reconstituting ability

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Varnum-Finney, Barbara, Brashem-Stein, Carolyn, Bernstein, Irwin D.·2003·Blood

Abstract

We investigated whether combined signaling induced by engineered Notch ligands and hematopoietic growth factors influences hematopoietic stem-cell differentiation. We show that incubation of murine marrow precursors with Delta1ext-IgG, a Notch ligand consisting of the Delta1 extracellular domain fused to the Fc portion of human immunoglobulin G1 (IgG1), and growth factors stem cell factor (SCF), interleukin 6 (IL-6), IL-11, and Flt3-l inhibited myeloid differentiation and promoted a several-log increase in the number of precursors capable of short-term lymphoid and myeloid repopulation. Addition of IL7 promoted early T-cell development, whereas addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) led to terminal myeloid differentiation. These results support a role for combinatorial effects by Notch and cytokine-induced signaling pathways in regulating hematopoietic cell fate and suggest the usefulness of Notch ligand in increasing hematopoietic precursor numbers for clinical stem-cell transplantation.

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Metadata

Authors
Varnum-Finney, B., Brashem-Stein, C., & Bernstein, I. D.
Venue
Blood
Published
2003-03-01
Volume
101
Issue
5
Pages
1784-1789
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
OpenAlex
W2051292725
Cited by
267
References
0
FWCI
10.09
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Combined effects of Notch signaling and cytokines induce a multiple log increase in precursors with lymphoid and myeloid reconstituting ability. https://app.cochat.ai/papers/10.1182/blood-2002-06-1862
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Varnum-Finney, B., Brashem-Stein, C., & Bernstein, I. D. (2003). Combined effects of Notch signaling and cytokines induce a multiple log increase in precursors with lymphoid and myeloid reconstituting ability. Blood. https://doi.org/10.1182/blood-2002-06-1862

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